.beta.-lactames are enzymes which open the .beta.-lactam ring of such antibiotics as penicillins and cephalosporins to yield products which are devoid of antibacterial activity. Clavulanic acid or 3-(.beta.-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo [3,2,0]heptane-2-carboxylic acid, including its pharmaceutically acceptable salts and esters, has now been well-recognized as a medium potency antibiotic which inhibits the production of .beta.-lactam enzymes, thereby enhancing the efficacy of .beta.-lactam antibiotics.
In particular, the combination of clavulanic acid and amoxycillin has been shown to be particularly effective against .beta.-lactams. The latter antibiotic is usually combined in a relatively large weight excess with the clavulanic acid to yield various pharmaceutical compositions. Dry, unit-dose compressed tablets for oral administration are just one example.
Unfortunately, in the preparation of many of these compositions the art has necessitated the inclusion of a complex formulation of excipients, including binders, glidants, disintegrants and even desiccants, etc. to yield a pharmaceutically acceptable carrier. This is in part due to the fact that clavulanate is a highly hygroscopic material which is highly unstable in aqueous media. Methods of formulation must therefore ensure that the product can retain its potency during storage, and yet can subsequently yield satisfactory dissolution rates. One such process is disclosed in WO 92/19227 and mandates the inclusion of both an intra-cellular and an extra-cellular disintegrant. Another process which is described in U.S. Pat. No. 4,537,887 specifies the inclusion of an edible desiccant within the composition itself. Other processes warrant the inclusion of a desiccant within a container housing the amoxycillin/clavulanate combination. In this regard, U.S. Pat. Nos. 4,301,149 and 4,441,609 are particularly salient.
What is therefore needed in the art is an improved tablet composition containing a .beta.-lactam antibiotic such as amoxicillin and a .beta.-lactamase inhibitor such as clavulanic acid which is simpler to manufacture and is highly moisture-resistant, and yet still presents a potent combination against .beta.-lactames.